ABSTRACT:
AIM: These guidelines for the treatment of psoriasis have been developed by the Psoriasis Research Group of the French Society of Dermatology with the aim of providing updated decision-making algorithms for the systemic treatment of adult patients with moderate-to-severe psoriasis. METHODS: Our algorithms were generated after rigorous evaluation of existing guidelines on the treatment of psoriasis and of publications concerning new systemic treatments, not yet incorporated into existing guidelines. A total of nine existing guidelines and 53 publications related to new systemic treatments were found to meet our criteria for use in generating the algorithms. RESULTS: We propose two new algorithms to assess therapeutic response, both of which incorporate emerging criteria for evaluating treatment goals. Updated therapeutic strategy algorithms, incorporating both established and new systemic therapies, were also generated for the treatment of plaque psoriasis and psoriatic arthritis, together with recommendations for the treatment of particular forms of psoriasis and treatment of patients with comorbidities.

ABSTRACT:
These guidelines were developed by the psoriasis research group of the French Society of Dermatology with the aim of providing updated decision-making algorithms for the systemic treatment of adult patients with moderate-to-severe psoriasis. Our algorithms were generated after rigorous evaluation of existing guidelines on the treatment of psoriasis and of publications concerning new systemic treatments, not yet incorporated into existing guidelines. A total of nine existing guidelines and 53 publications related to new systemic treatments were found to meet our criteria for use in the generation of the algorithms. We have proposed two new algorithms to assess therapeutic responses, both of which incorporate emerging criteria for evaluating treatment goals. Updated therapeutic strategy algorithms, incorporating both established and new systemic therapies, were also generated for the treatment of plaque psoriasis and psoriatic arthritis, together with recommendations for the treatment of particular forms of psoriasis and treatment of patients with comorbidities.

ABSTRACT:
Homozygous or compound heterozygous IL36RN gene mutations underlie the pathogenesis of psoriasis-related pustular eruptions including generalized pustular psoriasis, palmoplantar pustular psoriasis, acrodermatitis continua of Hallopeau, and acute generalized exanthematous pustular eruption. We identified two unreported IL36RN homozygous mutations (c.41C>A/p.Ser14X and c.420_426del/p.Gly141MetfsX29) in patients with familial generalized pustular psoriasis. We analyzed the impact of a spectrum of IL36RN mutations on IL-36 receptor antagonist protein by using site-directed mutagenesis and expression in HEK293T cells. This enabled us to differentiate null mutations with complete absence of IL-36 receptor antagonist (the two previously unreported mutations, c.80T>C/p.Leu27Pro, c.28C>T/p.Arg10X, c.280G>T/p.Glu94X, c.368C>G/p.Thr123Arg, c.368C>T/p.Thr123Met, and c.227C>T/p.Pro76Leu) from mutations with decreased (c.95A>G/p.His32Arg, c.142C>T/p.Arg48Trp, and c.308C>T/p.Ser113Leu) or unchanged (c.304C>T/p.Arg102Trp and c.104A>G/p.Lys35Arg) protein expression. Functional assays measuring the impact of mutations on the capacity to repress IL-36-dependent activation of the NF-κB pathway showed complete functional impairment for null mutations, whereas partial or no impairment was observed for other mutations considered as hypomorphic. Finally, null mutations were associated with severe clinical phenotypes (generalized pustular psoriasis, acute generalized exanthematous pustular eruption), whereas hypomorphic mutations were identified in both localized (palmoplantar pustular psoriasis, acrodermatitis continua of Hallopeau) and generalized variants. These results provide a preliminary basis for genotype-phenotype correlation in patients with deficiency of the IL-36Ra (DITRA), and suggest the involvement of other factors in the modulation of clinical expression.

ABSTRACT:
BACKGROUND: There are limited data regarding the long-term continuation with biological therapy for patients with psoriasis. In particular, the reasons for secukinumab discontinuation have not been thoroughly investigated. AIM: To better ascertain the real-life continuation of secukinumab in psoriasis, we conducted a retrospective study to evaluate the incidence, causes and factors of secukinumab discontinuation in patients with psoriasis. METHODS: All patients treated with secukinumab for psoriasis in the Department of Dermatology (Toulouse University and Larrey Hospital, Toulouse, France), between September 2011 and June 2017, were enrolled in the study. RESULTS: Of the 91 patients in the study, 22 (24.2%) discontinued secukinumab. In 14 (15%) patients, the discontinuation was due to loss of efficacy. Two patients stopped treatment because they planned a pregnancy and five patients stopped because of adverse events. A longer disease duration (P = 0.01) and presence of palmoplantar psoriasis (P = 0.01) seem to be predictive factors for treatment failure. Patients reaching 90 or 100% improvement in Psoriasis Area and Severity Index (PASI90 and PASI100, respectively) at weeks 12-16 had a lower risk of long-term treatment discontinuation compared with patients who had less complete clearance (P = 0.04). CONCLUSION: Long-term persistence of secukinumab appears to be good, as only 24.2% (n = 22) of the patients in this study discontinued secukinumab over the follow-up period. Loss of efficacy prompted discontinuation in about 14% of patients by the 2-year follow-up. Persistence appears to be lower in patients with palmoplantar psoriasis and in patients previously exposed to many systemic treatments. Optimal therapeutic response at 12-16 weeks as defined by reaching PASI90-100 seems to be predictive of long-term treatment persistence.

ABSTRACT:
Compounded topical preparations (CTP) were used to treat psoriasis until the last century and have disappeared from guidelines. The present authors report two severe psoriasis patients who were treated with CTP. A man had psoriasis with a PASI of 23 and a body surface area (BSA) of 43%. He had been using daily for several weeks a CTP including minoxidil, clobetasol propionate and hydroxyprogesterone formulated in an alcohol based vehicle. A woman suffered from psoriasis with an annular inflammatory pattern and a central healing. The PASI was 20 and the BSA was 30%. She had been using a CTP daily for 4 months including resorcinol, salicylic acid, 0.05% tretinoin cream, bethamethasone dipropionate cream. Until the 1970s, the dermatological textbooks recommended to treat severe psoriasis with CTP. Nowadays, CTP are considered outdated because of the large therapeutic armamentarium. The stability and benefit risks of the CTP used here were not documented. The use of CTP in psoriasis should be regulated and must be evidence based. Strict protocol and stability evaluation for preparations must be confirmed prior to compounding.

ABSTRACT:
BACKGROUND: Palmoplantar pustular psoriasis is a clinical psoriasis variant characterised by a high impact on quality of life and poor response to biologics approved for plaque type psoriasis.The recombinant interleukin-1 (IL-1) receptor antagonist anakinra has been recently used for the treatment of isolated refractory cases of generalised pustular psoriasis with contrasted results. OBJECTIVES: To report the clinical response in two patients treated with anakinra as salvage therapy in two patients with severe palmoplantar pustular psoriasis refractory to currently available antipsoriatic systemic therapies. METHODS: Anakinra was given subcutaneously at the daily dose of 100 mg, and clinical response was evaluated using the palmoplantar psoriasis area and severity index (PPPASI). RESULTS: Only partial and transient responses were observed in both patients, who had to stop anakinra due to lack of efficacy and to side effects. CONCLUSION: Anakinra appears to provide only partial clinical improvement in refractory palmoplantar pustular psoriasis. Prospective clinical studies on larger populations are warranted to investigate more accurately both efficacy and safety of IL-1-inhibiting strategies in pustular psoriasis.

ABSTRACT: We published in 2019 in the Journal of the European Academy of Dermatology and Venereology (JEADV) the first French guidelines on the use of systemic treatments for moderate-to-severe psoriasis in adults

ABSTRACT:
The identification of loss-of-function mutations of the IL36RN gene encoding the interleukin-36 receptor antagonist (IL-36Ra) in generalized pustular psoriasis (GPP) emphasized the key role of this pathway in skin innate immunity and systemic inflammation. It has been previously shown in vitro that removal of the N-terminal amino acid IL36Ra (M1) is critical to its biological activity, but the in vivo contribution of this processing remains unknown. We report herein a new homozygous (c4G>T, pV2F) missense IL36RN mutation segregating in a family with three GPP-affected patients. The V2F mutation does not alter IL-36Ra protein expression but was devoid of any antagonist activity. Mass spectrometry showed that the V2F IL-36Ra mutant retains its first N-terminal methionine. These results provide the first in vivo demonstration that removal of N-terminal methionine of native IL-36Ra is a mandatory step to reach optimal antagonist activity and to prevent sustained skin and systemic inflammation in humans.